Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians

 Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years. Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/10⁶ cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/10⁶ cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians (P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity. However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population (51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity. Received: 5 September 1997 / Accepted: 10 November 1997     

Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.     

海南百岁老人12项肥胖相关指标与全因死亡的关联研究

目的描述和分析BMI、腰围、腰臀比、腰高比、小腿围、腰围小腿围比值(WCR)、脂质蓄积指数(LAP)、内脏脂肪指数(VAI)、中国内脏脂肪指数(CVAI)、身体形态指数、中国身体形态指数(CABSI)和身体圆度指数与海南百岁老人全因死亡间的关联。方法整群抽样方法抽取的海南百岁老人共1 002人。随访时间的M(Q1, Q3)为4.16(1.31, 5.04)年, 结局为全因死亡, 使用Cox比例风险回归分析各肥胖相关身体测量指标与全因死亡的关联, 并使用受试者工作特征曲线曲线下面积(AUC)进行比较。结果总人群中小腿围对全因死亡的判定能力最强, AUC为0.61(95%CI:0.57～0.64), 分性别结果与总人群一致(P<0.05)。WCR次之(AUC为0.58), 再次是BMI、LAP和腰围, AUC分别为0.55、0.55和0.54, 而CABSI、腰臀比和VAI的判定能力较弱, AUC分别为0.51、0.50和0.50。结论本研究比较了12项肥胖相关指标与海南百岁老人全因死亡间的关联, 发现小腿围的预测判定能力最好, 且呈剂量反应关系, 提示可作为长寿老人死亡风险预测的参...     

Cancer in the oldest old

Our previous work revealed that 88% of centenarians delay or escape the age-related lethal diseases cardiac disease, stroke and diabetes. In the cases of those having a history of cancer we have observed anecdotes of centenarians presenting with large primary tumors that would have otherwise been expected to have metastasized and to have been lethal. However, these tumors were removed without consequence. To better understand the relationship between cancer and exceptional longevity, we quantified age of cancer diagnoses, life-time clinically evident cancer prevalence, tobacco use and family histories through medical record review and interviews. One thousand one hundred and forty-three subjects were studied revealing 20% (N=152) of female and 22% (N=80) of male centenarians with a history of non-skin cancer. The most common cancers were prostate (11.7% of males), breast (8.2% of females), and colon (5.7%). The average age of diagnosis was 80.5 years compared to 63.2 years in the general population according to National Cancer Institute SEER data. Similar delays were noted when age of onset was examined according to specific type of cancer. In conclusion, the age of diagnosis of cancer is relatively delayed in those who live to 100 years. Some cancers are very rare among these individuals suggesting that there are certain cancers that may be incompatible with survival to extreme old age.     

Hip fractures in centenarians

The centenarian population is increasing yet there is little about their morbidity and mortality rates following hip fracture. The aim was to review centenarians treated for proximal femoral fractures in Edinburgh describing treatment outcomes in relation to mortality, walking ability and residential status comparing centenarians with a the more typical hip fracture population. In this retrospective review, 18 centenarians sustaining hip fractures in Edinburgh between 1998 and 2002 were compared to 18 randomly selected "normal" hip fracture patients aged 75-83 years. Centenarian in-hospital, 1 and 4 month mortality was 11.1, 33.3 and 50%, respectively, versus 0, 0 and 5.6% in the normal group. Centenarian 4 month mortality was significantly greater than that of the normal group (Fisher's Exact Test, P = 0.00723). A total of 22.2% of centenarians regained pre-fracture walking ability compared to 58.8% of the normal patients. A total 28.6% of centenarians could continue living independently post-fracture compared to 69.2% of the normal group.     

Characteristics of centenarians’ lifestyles and their contribution to life satisfaction: A case study conducted on Hainan Island

BackgroundCentenarians represent an intriguing model for healthy aging. They appear to have adapted well to their lives and are likely to be influenced by previous lifestyle habits, and their life satisfaction is influenced by mental and psychological health.ObjectiveThe aim of this study is to explore centenarians’ lifestyles by sex and their potential contribution to life satisfaction.MethodIn order to examine the common characteristics of centenarians in Hainan and the potential differences between men and women, a cross-sectional survey was conducted with 223 cognitively-intact Chinese centenarians. We also explored the association between life satisfaction and other physical factors using binary logistic regression and principal component analysis.ResultsThe results provided supplementary evidence indicating that women tended to live longer than men. However, the difference in life satisfaction observed between the sexes was not obvious (p = 0.659). The proportion of physical factors between each sex showed a similar trend in distribution. Most centenarians’ lifestyles were similar, in that they followed a light diet and did not smoke or drink alcohol. Centenarians in better physical condition and with higher self-assessment, as well as those with “alcohol and tobacco habits,” were more satisfied with their life. Of the factors examined in the binary logistic regression, sleep satisfaction was the only factor significantly positively correlated with life satisfaction (p < .01).ConclusionThe research findings elucidated physiological and psychological health in centenarians and provided a model of healthy aging strategies for reference purposes.     

海南百岁老人中肥胖相关指标与抑郁症状风险的关联研究

目的分析百岁老人中腰围、BMI、腰臀比、腰高比、小腿围和腰围小腿围比值(WCR)与其抑郁症状风险间的关联。方法纳入全样本调查的海南百岁老人共1002人。使用GDS-15进行抑郁症状相关风险的调查,使用多元线性回归和logistic回归分析各人体测量指标与抑郁症状风险间的关联强度。结果校正人口学特征(性别、年龄、民族、婚姻状况、文化程度和居住类型)以及生活方式(吸烟和饮酒)相关变量后,总人群中BMI、腰围、腰臀比、腰高比、小腿围和WCR与GDS-15关联的标准β值分别为-0.069、-0.032、0.009、-0.009、-0.099和0.060,其中关于上述β值的检验P值中BMI和小腿围<0.05。随小腿围增加,百岁老人的抑郁症状风险随之降低,OR=0.94(95%CI:0.90~0.98)。而logistic回归分析中显示,随着小腿围的减少和WCR的增加,抑郁症状的风险逐步增加,趋势P值分别为0.038和0.042。结论百岁老人中,中心肥胖(腰围、WCR)与外周肥胖(小腿围)对于抑郁症状具有不同关联,百岁女性中小腿围增加是其抑郁症状风险的保护因素,应关注小腿围较低的老年女性的心理健康问题。     

海南百岁老人主要健康指标及其与生存质量的关联研究

百岁老人作为研究健康老龄化的"模板人群", 探索其健康长寿特征及其相关影响因素, 有助于探讨我国人口老龄化背景下实现健康长寿的可能路径。近年来, 包括中国海南百岁老人队列研究(CHCCS)在内的长寿人群观察性研究报道了百岁老人主要健康特征与生存质量的关联。本文旨在综述CHCCS近年来发现的相关研究证据并结合国内同类研究结果进行分析。其中主要健康指标包括血压、血脂、血糖、血红蛋白、身体测量指标和肾功能等;生存质量及健康结局包括饮食、营养、健康相关生活质量、日常活动能力、老年综合征等。以期为制定健康老龄化政策提供相关人群流行病学证据。     

海南百岁老人营养状况对全因死亡影响的前瞻性队列研究

目的探讨海南百岁老人营养状况与全因死亡风险之间的关系。方法利用中国海南百岁老人队列研究2014-2021年调查数据, 本研究共纳入1 002名基线资料完整的海南百岁老人, 随访其生存与死亡结局。根据简易营养评估量表将百岁老人的营养状况分为营养良好(12～14分)、营养不良风险(8～11分)和营养不良(0～7分)3组。利用Kaplan-Meier曲线评估百岁老人的生存状况;利用Cox比例风险回归模型评估营养状况与全因死亡之间的关联。结果 2021年5月31日随访结束后, 共发现522名百岁老人死亡, 7年全因死亡率为52.10%(522/1 002)。与营养良好组相比, 营养不良导致的平均减寿为0.62年。生存分析显示, 营养不良组全因死亡率高于其他组(χ2=16.45, P<0.001)。多因素Cox比例风险回归分析结果显示, 与营养良好的百岁老人相比, 营养不良组全因死亡风险更高(HR=1.65, 95%CI:1.18～2.31)。亚组分析发现女性百岁老人该关联更为显著。结论营养不良与海南百岁老人高全因死亡风险相关, 提示应及时评估和关注百岁老人特别是女性老人营养状况对其健康长...